Table 2.

List of recent studies investigating nanoparticle-mediated delivery of tumor antigen(s) either alone or in combination with adjuvant(s)/DC-targeting moieties for cancer therapeutic vaccination

Carrier	Loaded with	Study type	Outcomea	References
Liposome	Hsp70 peptide complex	Breast cancer mouse model	Enhanced immune response	[165]
Liposome	MUC1 peptide, TLR4 ligand	Phase I–II–III studies	Phase I studies: vaccine was well tolerated; phase II study in NSCLC: survival improvement; Phase III study in NSCLC: only improvement observed was in concurrent chemoradiotherapy with a 10.2 month improvement in median survival	[96, 97, 101, 103]
Liposome	HLA-B7 and β2-microglobulin DNA	Phase II-III studies	Phase II study in metastatic melanoma had a positive outcome, but phase III study failed and product is currently discontinued	[102, 104]
Liposome	NY-ESO-1, MAGE-A3, tyrosinase and TPTE RNA	Phase I study	Positive outcome in all 3 patients tested. Recruitment of more patients is currently undergoing	[98]
Liposome	Mix of different peptides	Phase I study	Phase I trial positive outcome, with induced de novo and specific T cell response	[99, 100]
Liposome	SOCS1, A20 siRNA	Mouse lymphoma model	Drastic enhancement in cytokine production resulting in significant tumor suppression	[166]
Liposome	E7 HPV	TC-1 lung mouse model	Induced specific CD8+T cell response and Treg inhibition	[167]
Liposome	OVA, TLR3/9 ligands	C57BL/6 mouse model	Increased CD8+ T cell response	[123]
γ-PGA/Polylysine	Empty or ovalbumin	C57BL/6 mouse model	Comparative study: PGA has intrinsic immunogenic properties and induced a stronger immune response than polylysine when both loaded with ovalbumin	[160]
γ-PGA	Ovalbumin	C57BL/6 mouse model	γ-PGA immunogenic properties are TLR4 signalling-dependent	[168]
Cationic polymers (PE/C32)	CD40 ligand DNA, CpG + poly(I:C)	B16-F10 melanoma mouse model	Comparative study: C32 polimer was superior to PE. TLR ligands had a synergistic effect in triggering immune response	[124]
PLGA	WTL	In vitro	Co-culture of patient TILs with patient DCs pulsed with autologous WTL-NPs resulted in higher IFN-γ and lower IL-10 production compared to soluble WTL	[110, 111]
PLGA	WTL, CpG, polyI:C	TRAMP mouse model	Induced CTL response and tumor shrinkage	[112]
PLGA	WTL	In vitro	Increased T cell proliferation	[113]
PLGA	Ovalbumin TLR3/7 ligands; CD40, CD11c, or DEC-205 ab	C57BL/6 mouse model	NP coating with targeting molecules (CD40, CD11c or DEC-205 antibodies) induced a stronger immune response	[106]
PLGA	Ovalbumin, mannose	C57BL/6 mouse model	Decoration of ovalbumin-NPs with mannose moieties increased the efficiency of ovalbumin-specific CD4+ and CD8+ T cell responses	[107]
PLGA	TRP2180–188; TLR-4 ligand	B16-F10 melanoma mouse model	Immune stimulation in the tumor microenvironment, induction of antigen-specific CD8+ response	[108]
PLGA	Hgp10025–33 TRP2180–188	C57BL/6 mouse model	Increased antigen-specific T cell response	[109]
Cholesteryl pullulan	HER2 fragment; NY-ESO-1 protein	Phase I studies	Vaccine was well tolerated and induced antigen-specific immune responses	[114–116]
Chitosan	Ovalbumin, alginate	In vitro	Sugar-coated NP induced higher IFN-γ production in co-culture assays	[169]
Chitosan	WTL, mannose	B16 melanoma mouse model	Increased tumor growth inhibition	[117]
BSA/pyridine	Ovalbumin	In vitro	This type of nanogel had intrinsic adjuvant properties	[170]
Nanogel	Ovalbumin, galactose	B16-OVA mouse model	(pH-sensitive system) cytosolic antigen release; ROS production and increased MHC-I antigen presentation	[133]

γ-PGA poly(γ-glutamic acid), BSA bovine serum albumin, NP nanoparticle, NSCLC non-small-cell carcinoma, PLGA poly(lactic-co-glycolic acid), TLR toll-like receptor, TRAMP transgenic adenocarcinoma of the mouse prostate, WTL whole tumor lysate

^aCompared to free soluble agent, when applicable